This area of investigation began with the demonstration of monoclonal anti-MAG antibodies in patients with mixed sensory-motor polyneuropathies occurring in association with IgM paraproteinemia. It was subsequently demonstrated that these anti-MAG antibodies were all directed toward carbohydrate epitopes in MAG and cross-reacted with 19 to 28 kD glycoproteins of PNS myelin and a sphingoglycolipid, sulfate-3- glucuronyl paragloboside (SGPG). Monoclonal antibodies that are MAG/SGPG- negative in patients with IgM gammopathy and neuropathy frequently react with ganglioside antigens in nerve. In the current year, we have identified a patient with a predominantly sensory neuropathy and a monoclonal IgM antibody that binds strongly to G(D1b) ganglioside and some other minor gangliosides that also contain a disialosyl group. Interestingly, we had previously reported another patient with a sensory neuropathy that had an IgM monoclonal antibody that reacted with gangliosides containing disialosyl groups, although the fine specificity of that patient's antibody was somewhat different. Nevertheless, the findings suggest that antibodies of this general specificity may play a role in the pathogenesis of sensory neuropathies. Previous results from our laboratory and others had shown a strong correlation of high titer, monoclonal and polyclonal antibodies to G(M1) ganglioside with motor neuropathies. Moderately elevated antibodies to gangliosides were detected in a few cases of adrenoleukodystrophy but there was no correlation with the severity or nature of the clinical presentation to suggest that the antibodies played a role in the suspected, secondary autoimmune aspects of this genetic disease. It should be emphasized that our work and that of others indicate that serum antibodies in patients with neurological diseases should be analyzed both qualitatively by TLC overlay and quantitatively by ELISA since the pathogenic significance of antibodies to glycolipids appears to depend both on their specificity and titer. Several immortalized Schwann cell lines and a myelinating dorsal root ganglion tissue culture system have now been established and will be used to evaluate the possible cytotoxic or demyelinating effects of the human anti-glycolipid antibodies from neuropathy patients.